Objective:

The overall objective of the Southern California Particle Center (SCPC) is to investigate the mechanisms that produce the health effects associated with exposure to particulate matter (PM), and to understand how toxic mechanisms and resulting health effects vary with the source, chemical composition, and physical characteristics of PM.

The SCPC relies on a team of highly respected researchers committed to developing a strong multidisciplinary program to address the challenging public health issues posed by PM pollution, with a focus on the unique urban setting of the Los Angeles air basin. Our research projects are united by a hypothesis that chemical composition and physical characteristics related to PM sources determine the toxicity and exposure-response of PM. Variations in exposure according to source, season, and location influence the resulting human health responses. The principal mechanistic hypothesis of the SCPC is that many health effects associated with PM exposure including adverse respiratory and cardiovascular outcomes derive from the induction of oxidative stress by reactive chemical species (organic or inorganic) in PM. Oxidative stress and inflammatory responses related to asthma and atherosclerosis are a particular focus. Integral to our toxicological hypothesis is the role of antioxidant defense pathways that protect against the pro-inflammatory effects of PM.

The studies undertaken by the SCPC address research priorities in source linkages, susceptibility to PM, biological mechanisms for PM, and exposure-response relationships as identified by the U.S. Environmental Protection Agency (EPA). Our research to address these priorities is integrated across a wide variety of disciplines, including aerosol formation and characterization, advanced analytical chemistry, exposure assessment, chemical toxicology, genetic toxicology and immunology, animal toxicology, epidemiology and biostatistics. Linking the diverse research efforts into a coordinated whole is an overarching theme, as illustrated in the pictorial diagram of the five SCPC projects (Figure 1).

Figure 1.

Progress Summary:

The first months of the new Southern California Particle Center (SCPC) have been quite successful with all projects initiating their planned research. A major freeway sampling campaign was completed, which included high volume filter collections of coarse, fine, and ultrafine PM; analysis of polycyclic aromatic hydrocarbon (PAH) and tracer concentrations for emission factor calculations; collection of coarse, fine, and ultrafine PM to be used for chemical toxicology and in vitro studies; tandem differential mobility analyzer measurements of particle diameter/volatility; particle surface area measurements; and ultrafine mass chemical composition analyses. All of the above analyses resulting from the freeway campaign are completed or underway, and Project 1 has produced three manuscripts for publication. In Project 2, two in vivo animal studies of mice with genetic susceptibility to atherosclerosis (ApoE null and LDL receptor knockout mice) have been performed. ApoE null mice exposed to fine and ultrafine PM displayed increased atherosclerotic lesional area in the aorta compared to control animals, while PM exposure did not enhance lesions in mice that lack LDL receptors and were maintained on a Western Diet. Brain tissues from the ApoE mice displayed elevated expression levels of a key transcription factor. Further analyses of the biological samples collected from exposed and control mice in these experiments are underway. In vitro studies of particles have also advanced during year 1 of the SCPC, with a study from Project 2 that compared ambient ultrafines to a variety of commercial nanoparticles in cell-free and cellular assays designed to detect production of reactive oxygen species and oxidative toxicity in test cells. Project 3 completed the analysis of quinone species in particle and gaseous samples collected across the Los Angeles Basin, and reports that the concentration of some of the assayed species increases as the air mass ages, suggesting that these redox active compounds are photochemically produced. Two assays for reactive oxygen species were performed on a wide range of indoor and outdoor samples collected at retirement homes. Analysis of the freeway samples in redox and other assays is underway in the laboratories of Projects 2 and 3. Progress was reported on deciphering the mechanisms by which quinones may promote cellular changes, in a study showing increased activation of a key protein tyrosine kinase receptor in treated cells. Project 4 has followed 32 elderly people with coronary artery disease, with weekly blood draws. Glutathione Peroxidase-1, superoxide dismutase, hemoglobin and myeloperoxidase assays are underway. The protocols for determination of 8-isoprostane and the ratio of glutathione to reduced glutathione are being refined for successful application to the collected biological samples. A new Project 5 has been added to the SCPC. Project 5 developed a proposal and conducted preliminary measurements to support the design of a planned high volume sampling system for capturing both the particulate and vapor phase contaminants in a 500 m3 air sample. An instrumented van was used in studies of changes in ultrafine particles near freeways by taking Transmission Electron Microscopy (TEM) samples for morphological analysis of 50 nm mobility diameter particles. Results suggest that the aerosols were internally mixed. Year 1 summaries for the individual projects, containing results and findings, will follow.

Research Challenges. The SCPC did not experience any significant difficulties during the reporting period.

Individual Research Project Goals/Hypotheses Changes and Rationale. A new Project 5 has been added to the organization of the SCPC. In the original SCPC proposal, Dr. William Hinds had a role within Project 1, with Dr. Sioutas. Since that time, Dr. Hinds has introduced a proposal to take advantage of an opportunity for a jointly funded project with the SCPC and the California Air Resources Board. In Project 5, Dr. Hinds proposes to collect large scale samples of fine particles and volatile air components at three different locations: on a freeway to collect fresh traffic emissions of particles and gases; an urban source site not directly on a freeway, and an urban receptor site that will reflect photochemical aging of source emissions. The project utilizes a van equipped with a two person exposure chamber and instruments including CPC, SMPS, aethelometer, particle-bound PAH, PM-10, PM-2.5, NOx, CO2, CO, temperature, relative humidity, and GPS, and is jointly funded with the CARB study that seeks to evaluate a variety of short term measures of exposure and response including heart rate variability, and 26 cytokines and other blood factors before, after, and 20 hours after exposure to freeway or filtered air. The large scale samples will be evaluated in a variety of assays by Dr. Cho and his staff (Project 3). The Project 5 description will be submitted to EPA as a separate report.

The rationale underlying additional sample collections and expansion of scope for Project 3 is that SCPC studies completed during this first year of funding have shown that four quinone species are present in both particle and gaseous fractions of ambient air samples across the Los Angeles Basin, and are in fact at higher concentrations in the gaseous phase (please see the report for Project 3). Since quinone compounds contribute to the redox capacity of polluted air, an assessment of total exposure to redox active species requires simultaneous monitoring of both the particulate and gaseous phases at a location of interest. The expanded scope of Project 3 will enable total redox exposure assessment by collecting a set samples dedicated to redox assays, and large enough to meet the needs of the multiple redox and biological assays the SCPC has developed.

Year-1 Center Expenditure. There was a re-budget in the Administrative Core and Project 2. Pursuant to EPA guidelines, a detailed review of the Year-1 financials will be submitted on November 1, 2006.

Research Quality Assurance Requirement. In March 2006, Quality Management Project Plans (QMPP) were submitted to Dr. John Froines, SCPC Principal Investigator, by individual project leads. The documents are filed at the SCPC central management office at UCLA.

Future Activities:

Planned Year-2 Sampling Campaigns

Projects’ Year-2 efforts are in accord with the overall proposed sampling schedule, namely:

Relevant Websites:

Progress and Final Reports:

Subprojects under this Center:(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).R832413C001 Contribution of Primary and Secondary PM Sources to Exposure & Evaluation of Their Relative ToxicityR832413C002 Project 2: The Role of Oxidative Stress in PM-induced Adverse Health EffectsR832413C003 The Chemical Properties of PM and their Toxicological ImplicationsR832413C004 Oxidative Stress Responses to PM Exposure in Elderly Individuals With Coronary Heart DiseaseR832413C005 Ultrafine Particles on and Near Freeways

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.